Details for: SERPINB5

Gene ID: 5268

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SERPINB5

Ensembl ID: ENSG00000206075

Description: serpin family B member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • corneal epithelial cell CL0000575
    CSI 9.45
    rCSI 27.03%
    PRS 97.05
  • conjunctival epithelial cell CL1000432
    CSI 7.77
    rCSI 11.87%
    PRS 96.28
  • keratinocyte CL0000312
    CSI 7.47
    rCSI 6.26%
    PRS 96.33
  • epithelial cell CL0000066
    CSI 4.92
    rCSI 7.56%
    PRS 89.12
  • respiratory suprabasal cell CL4033048
    CSI 4.89
    rCSI 6.27%
    PRS 97.61
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 4.77
    rCSI 9.02%
    PRS 98.68
  • dendritic cell CL0000451
    CSI 3.53
    rCSI 4.35%
    PRS 96.15
  • respiratory basal cell CL0002633
    CSI 3.49
    rCSI 3.61%
    PRS 97.58
  • respiratory hillock cell CL4030023
    CSI 3.2
    rCSI 5.71%
    PRS 98.12
  • myoepithelial cell CL0000185
    CSI 2.99
    rCSI 7.56%
    PRS 97.98
  • basal cell of prostate epithelium CL0002341
    CSI 2.67
    rCSI 7.73%
    PRS 97.56
  • basal cell CL0000646
    CSI 2.49
    rCSI 3.33%
    PRS 95.49
  • foveolar cell of stomach CL0002179
    CSI 2.37
    rCSI 5.04%
    PRS 97.3
  • M cell of gut CL0000682
    CSI 2.36
    rCSI 2.5%
    PRS 97.25
  • lung ciliated cell CL1000271
    CSI 2.1
    rCSI 2.43%
    PRS 94.07
  • basal cell of epidermis CL0002187
    CSI 2.08
    rCSI 3.69%
    PRS 76.61
  • enteroendocrine cell CL0000164
    CSI 2.08
    rCSI 2.84%
    PRS 95.25
  • squamous epithelial cell CL0000076
    CSI 1.89
    rCSI 4.5%
    PRS 93.68
  • club cell CL0000158
    CSI 1.84
    rCSI 2.69%
    PRS 95.47
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.64
    rCSI 4.41%
    PRS 97.63
  • epithelial cell of urethra CL1000296
    CSI 1.28
    rCSI 32.31%
    PRS 97.28
  • epithelial cell of esophagus CL0002252
    CSI 1.13
    rCSI 11.21%
    PRS 94.62
  • basal cell of epithelium of trachea CL1000348
    CSI 0.92
    rCSI 6.51%
    PRS 96.82
  • hair follicular keratinocyte CL2000092
    CSI 0.79
    rCSI 13.72%
    PRS 96.32
  • Merkel cell CL0000242
    CSI 0.62
    rCSI 14.47%
    PRS 98.83

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SERPINB5](/details-gene/5268), also known as Maspin (Mammary Serine Protease Inhibitor), is a protein-coding gene located on chromosome 18q21.33. It belongs to the serpin superfamily of protease inhibitors, although its primary mechanism of action may be non-inhibitory ([Link](https://doi.org/10.1074/jbc.270.26.15832)). [SERPINB5](/details-gene/5268) is strongly associated with tumor suppression, particularly in epithelial tissues ([Link](https://doi.org/10.1126/science.8290962)). Its expression profile indicates a crucial role in maintaining the integrity and regulating the proliferation of various epithelial cell populations, including those in the cornea, skin, and mammary gland. Functionally, it is involved in processes such as `[Extracellular matrix organization](/details-go/GO:0030198)` and the `[Negative regulation of endopeptidase activity](/details-go/GO:0010951)`, consistent with its proposed role in controlling tissue architecture and cell behavior. ## Cellular Roles and Expression Landscape The expression pattern of [SERPINB5](/details-gene/5268) demonstrates a striking specificity for epithelial cell types across various tissues. **Overall**, its most significant expression is found in the `[corneal epithelial cell](/details-cell/CL0000575)` (CSI: 9.45), `[conjunctival epithelial cell](/details-cell/CL1000432)` (CSI: 7.77), and `[keratinocyte](/details-cell/CL0000312)` (CSI: 7.47), highlighting a fundamental role in the maintenance of stratified squamous epithelia exposed to the external environment. This epithelial-centric role extends to glandular and mucosal tissues. High significance scores are observed in `[basal-myoepithelial cell of mammary gland](/details-cell/CL0002324)` (CSI: 4.77), `[basal cell of prostate epithelium](/details-cell/CL0002341)` (CSI: 2.67), and respiratory cells such as `[respiratory suprabasal cell](/details-cell/CL4033048)` (CSI: 4.89) and `[respiratory basal cell](/details-cell/CL0002633)` (CSI: 3.49). This pattern suggests that [SERPINB5](/details-gene/5268) is a key molecular player in basal and myoepithelial compartments, which are critical for tissue homeostasis, regeneration, and structural support. Its presence in these specific cell types aligns with its documented tumor-suppressive functions in breast and prostate carcinomas. ## Pathways and Molecular Function [SERPINB5](/details-gene/5268) is annotated with the molecular function of `[serine-type endopeptidase inhibitor activity](/details-go/GO:0004867)`. However, research suggests that unlike typical inhibitory serpins, it may not undergo the conformational change required to inhibit proteases, pointing towards alternative mechanisms of action ([Link](https://doi.org/10.1074/jbc.270.26.15832)). Its function may instead be mediated through `[protein binding](/details-go/GO:0005515)`, as evidenced by its interaction with interferon regulatory factor 6 (IRF6) ([Link](https://doi.org/10.1074/jbc.m503523200)). This molecular activity translates into several key biological processes. Its involvement in `[Extracellular matrix organization](/details-go/GO:0030198)` and `[Morphogenesis of an epithelium](/details-go/GO:0002009)` is consistent with its high expression in epithelial barrier tissues and its tumor-suppressive role in preventing cell invasion. Furthermore, its participation in the `[Regulation of epithelial cell proliferation](/details-go/GO:0050678)` and `[Prostate gland morphogenesis](/details-go/GO:0060512)` directly supports its observed cellular expression in the basal cells of these glands. The protein is found in the `[Cytoplasm](/details-go/GO:0005737)` and is also secreted into the `[Extracellular space](/details-go/GO:0005615)`, allowing it to influence both intracellular signaling and the surrounding microenvironment. ## Research Directions The established role of [SERPINB5](/details-gene/5268) as a tumor suppressor whose expression is often lost during cancer progression, combined with its highly specific expression profile, provides fertile ground for further investigation. **Testable Hypotheses:** 1. Given its high expression in `[basal-myoepithelial cell of mammary gland](/details-cell/CL0002324)` and its known tumor-suppressive activity, the loss of [SERPINB5](/details-gene/5268) in this specific cell population may be a critical early event that disrupts epithelial polarity and facilitates the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer. 2. The tumor-suppressive function of [SERPINB5](/details-gene/5268) in `[keratinocyte](/details-cell/CL0000312)`s may not rely on protease inhibition but rather on its interaction with transcription factors like IRF6 ([Link](https://doi.org/10.1074/jbc.m503523200)). This interaction could be crucial for regulating gene expression programs that control cell adhesion and prevent the migratory phenotype associated with squamous cell carcinoma. **Proposed Experimental Approach:** To test the first hypothesis, a robust experimental plan would involve spatial transcriptomics and proteomics on a cohort of human DCIS and invasive breast cancer tissue samples. This would allow for the precise quantification of [SERPINB5](/details-gene/5268) expression specifically within the myoepithelial cell layer. Concurrently, CRISPR-Cas9 could be used to selectively knock out [SERPINB5](/details-gene/5268) in myoepithelial cells within 3D co-culture organoid models, containing both luminal and myoepithelial cells. The effect of its deletion on organoid structure, luminal cell proliferation (via Ki-67 staining), and invasion into the surrounding matrix could then be directly assessed using advanced microscopy and biochemical assays. **Therapeutic Potential:** As a tumor suppressor, [SERPINB5](/details-gene/5268) itself is not a direct target for inhibition. Instead, therapeutic strategies would focus on re-expression or functional restoration in cancer cells where it has been silenced. This presents a significant challenge but could be conceptually approached through epigenetic drugs aimed at reversing promoter methylation (a common mechanism for its silencing) or through advanced gene delivery systems. Given the potential for its function to be mediated by protein-protein interactions, small molecules designed to mimic its binding interface or stabilize its active conformation could also represent a novel therapeutic avenue. Such an approach would require a deep understanding of its non-inhibitory structural biology.

Genular Protein ID: 1954691440

Symbol: SPB5_HUMAN

Name: Serpin B5

UniProtKB Accession Codes:

P36952 B2R6Y4 Q6N0B4 Q8WW89

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8290962

Title: Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.

PubMed ID: 8290962

DOI: 10.1126/science.8290962

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16177791

Title: DNA sequence and analysis of human chromosome 18.

PubMed ID: 16177791

DOI: 10.1038/nature03983

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 7797587

Title: The tumor suppressor maspin does not undergo the stressed to relaxed transition or inhibit trypsin-like serine proteases. Evidence that maspin is not a protease inhibitory serpin.

PubMed ID: 7797587

DOI: 10.1074/jbc.270.26.15832

PubMed ID: 16049006

Title: Mammary serine protease inhibitor (Maspin) binds directly to interferon regulatory factor 6: identification of a novel serpin partnership.

PubMed ID: 16049006

DOI: 10.1074/jbc.m503523200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 15760906

Title: The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix.

PubMed ID: 15760906

DOI: 10.1074/jbc.m412043200

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

Sequence Information:

  • Length: 375
  • Mass: 42100
  • Checksum: 9F24E18505912804
  • Sequence:
    • MDALQLANSA FAVDLFKQLC EKEPLGNVLF SPICLSTSLS LAQVGAKGDT ANEIGQVLHF 
ENVKDVPFGF QTVTSDVNKL SSFYSLKLIK RLYVDKSLNL STEFISSTKR PYAKELETVD 
FKDKLEETKG QINNSIKDLT DGHFENILAD NSVNDQTKIL VVNAAYFVGK WMKKFSESET 
KECPFRVNKT DTKPVQMMNM EATFCMGNID SINCKIIELP FQNKHLSMFI LLPKDVEDES 
TGLEKIEKQL NSESLSQWTN PSTMANAKVK LSIPKFKVEK MIDPKACLEN LGLKHIFSED 
TSDFSGMSET KGVALSNVIH KVCLEITEDG GDSIEVPGAR ILQHKDELNA DHPFIYIIRH 
NKTRNIIFFG KFCSP